Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTTNLMVM)

DOT Name Superkiller complex protein 2 (SKIC2)
Synonyms Ski2; EC 3.6.4.13; Helicase-like protein; HLP
Gene Name SKIC2
Related Disease
Trichohepatoenteric syndrome 2 ( )
Trichohepatoenteric syndrome ( )
UniProt ID
SKI2_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
PDB ID
7QDR; 7QDS; 7QDY; 7QDZ; 7QE0
EC Number
3.6.4.13
Pfam ID
PF00270 ; PF08148 ; PF00271 ; PF21408 ; PF13234 ; PF17911
Sequence
MMETERLVLPPPDPLDLPLRAVELGCTGHWELLNLPGAPESSLPHGLPPCAPDLQQEAEQ
LFLSSPAWLPLHGVEHSARKWQRKTDPWSLLAVLGAPVPSDLQAQRHPTTGQILGYKEVL
LENTNLSATTSLSLRRPPGPASQSLWGNPTQYPFWPGGMDEPTITDLNTREEAEEEIDFE
KDLLTIPPGFKKGMDFAPKDCPTPAPGLLSLSCMLEPLDLGGGDEDENEAVGQPGGPRGD
TVSASPCSAPLARASSLEDLVLKEASTAVSTPEAPEPPSQEQWAIPVDATSPVGDFYRLI
PQPAFQWAFEPDVFQKQAILHLERHDSVFVAAHTSAGKTVVAEYAIALAQKHMTRTIYTS
PIKALSNQKFRDFRNTFGDVGLLTGDVQLHPEASCLIMTTEILRSMLYSGSDVIRDLEWV
IFDEVHYINDVERGVVWEEVLIMLPDHVSIILLSATVPNALEFADWIGRLKRRQIYVIST
VTRPVPLEHYLFTGNSSKTQGELFLLLDSRGAFHTKGYYAAVEAKKERMSKHAQTFGAKQ
PTHQGGPAQDRGVYLSLLASLRTRAQLPVVVFTFSRGRCDEQASGLTSLDLTTSSEKSEI
HLFLQRCLARLRGSDRQLPQVLHMSELLNRGLGVHHSGILPILKEIVEMLFSRGLVKVLF
ATETFAMGVNMPARTVVFDSMRKHDGSTFRDLLPGEYVQMAGRAGRRGLDPTGTVILLCK
GRVPEMADLHRMMMGKPSQLQSQFRLTYTMILNLLRVDALRVEDMMKRSFSEFPSRKDSK
AHEQALAELTKRLGALEEPDMTGQLVDLPEYYSWGEELTETQHMIQRRIMESVNGLKSLS
AGRVVVVKNQEHHNALGVILQVSSNSTSRVFTTLVLCDKPLSQDPQDRGPATAEVPYPDD
LVGFKLFLPEGPCDHTVVKLQPGDMAAITTKVLRVNGEKILEDFSKRQQPKFKKDPPLAA
VTTAVQELLRLAQAHPAGPPTLDPVNDLQLKDMSVVEGGLRARKLEELIQGAQCVHSPRF
PAQYLKLRERMQIQKEMERLRFLLSDQSLLLLPEYHQRVEVLRTLGYVDEAGTVKLAGRV
ACAMSSHELLLTELMFDNALSTLRPEEIAALLSGLVCQSPGDAGDQLPNTLKQGIERVRA
VAKRIGEVQVACGLNQTVEEFVGELNFGLVEVVYEWARGMPFSELAGLSGTPEGLVVRCI
QRLAEMCRSLRGAARLVGEPVLGAKMETAATLLRRDIVFAASLYTQ
Function
Helicase component of the SKI complex, a multiprotein complex that assists the RNA-degrading exosome during the mRNA decay and quality-control pathways. The SKI complex catalyzes mRNA extraction from 80S ribosomal complexes in the 3'-5' direction and channels mRNA to the cytosolic exosome for degradation. SKI-mediated extraction of mRNA from stalled ribosomes allow binding of the Pelota-HBS1L complex and subsequent ribosome disassembly by ABCE1 for ribosome recycling. In the nucleus, the SKI complex associates with transcriptionally active genes in a manner dependent on PAF1 complex (PAF1C).
KEGG Pathway
R. degradation (hsa03018 )
Reactome Pathway
mRNA decay by 3' to 5' exoribonuclease (R-HSA-429958 )
Association of TriC/CCT with target proteins during biosynthesis (R-HSA-390471 )

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Trichohepatoenteric syndrome 2 DISDH8OZ Definitive Autosomal recessive [1]
Trichohepatoenteric syndrome DISL3ODF Supportive Autosomal recessive [2]
------------------------------------------------------------------------------------
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
3 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Ciclosporin DMAZJFX Approved Ciclosporin increases the expression of Superkiller complex protein 2 (SKIC2). [3]
Temozolomide DMKECZD Approved Temozolomide increases the expression of Superkiller complex protein 2 (SKIC2). [5]
Bisphenol A DM2ZLD7 Investigative Bisphenol A increases the expression of Superkiller complex protein 2 (SKIC2). [7]
------------------------------------------------------------------------------------
3 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Arsenic DMTL2Y1 Approved Arsenic affects the methylation of Superkiller complex protein 2 (SKIC2). [4]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 decreases the phosphorylation of Superkiller complex protein 2 (SKIC2). [6]
Coumarin DM0N8ZM Investigative Coumarin decreases the phosphorylation of Superkiller complex protein 2 (SKIC2). [6]
------------------------------------------------------------------------------------

References

1 Flexible and scalable diagnostic filtering of genomic variants using G2P with Ensembl VEP. Nat Commun. 2019 May 30;10(1):2373. doi: 10.1038/s41467-019-10016-3.
2 SKIV2L mutations cause syndromic diarrhea, or trichohepatoenteric syndrome. Am J Hum Genet. 2012 Apr 6;90(4):689-92. doi: 10.1016/j.ajhg.2012.02.009. Epub 2012 Mar 22.
3 Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
4 Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
5 Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
6 Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
7 Bisphenol A Exposure Changes the Transcriptomic and Proteomic Dynamics of Human Retinoblastoma Y79 Cells. Genes (Basel). 2021 Feb 11;12(2):264. doi: 10.3390/genes12020264.